Department of Pharmaceutical Chemistry, Government College University, Faisalabad 38000, Pakistan.
Department of Pharmacy, The Women University, Multan 60000, Pakistan.
Molecules. 2023 Aug 3;28(15):5865. doi: 10.3390/molecules28155865.
The aim of this study was to investigate the disruptions of metabolic pathways induced by bisphenol A (BPA) and explore the potential therapeutic intervention provided by resveratrol (RSV) in mitigating these disruptions through the modulation of biochemical pathways. Wistar albino rats were divided into three groups: group 1 served as the control, group 2 received 70 mg/Kg of BPA, and group 3 received 70 mg/kg of BPA along with 100 mg/Kg of RSV. After the treatment period, various biomarkers and gene expressions were measured to assess the effects of BPA and the potential protective effects of RSV. The results revealed that BPA exposure significantly increased the serum levels of α-amylase, α-glucosidase, G6PC, insulin, HbA1c, HMG-CoA reductase, FFAs, TGs, DPP-4, MDA, and proinflammatory cytokines such as TNF-α and IL-6. Concurrently, BPA exposure led to a reduction in the levels of antioxidant enzymes such as catalase (CAT), glutathione peroxidase (GPx), and superoxide dismutase (SOD), as well as GLUT4 and HDL cholesterol. However, the administration of RSV along with BPA significantly ameliorated these alterations in the biomarker levels induced through BPA exposure. RSV treatment effectively reduced the elevated levels of α-amylase, α-glucosidase, G6PC, insulin, HbA1c, HMG-CoA reductase, FFAs, TGs, DPP-4, MDA, and proinflammatory cytokines, while increasing the levels of antioxidant enzymes, GLUT4, and HDL cholesterol. Furthermore, BPA exposure suppressed the mRNA expression of glucokinase (GCK), insulin-like growth factor 1 (IGF-1), and glucose transporter 2 (GLUT2) and up-regulated the mRNA expression of uncoupling protein 2 (UCP2), which are all critical biomarkers involved in glucose metabolism and insulin regulation. In contrast, RSV treatment effectively restored the altered mRNA expressions of these biomarkers, indicating its potential to modulate transcriptional pathways and restore normal metabolic function. In conclusion, the findings of this study strongly suggest that RSV holds promise as a therapeutic intervention for BPA-induced metabolic disorders. By mitigating the disruptions in various metabolic pathways and modulating gene expressions related to glucose metabolism and insulin regulation, RSV shows potential in restoring normal metabolic function and counteracting the adverse effects induced by BPA exposure. However, further research is necessary to fully understand the underlying mechanisms and optimize the dosage and duration of RSV treatment for maximum therapeutic benefits.
本研究旨在探讨双酚 A(BPA)引起的代谢途径紊乱,并通过调节生化途径,探索白藜芦醇(RSV)在减轻这些紊乱方面的潜在治疗干预作用。将 Wistar 白化大鼠分为三组:第 1 组为对照组,第 2 组给予 70mg/kg 的 BPA,第 3 组给予 70mg/kg 的 BPA 加 100mg/kg 的 RSV。治疗期结束后,测量各种生物标志物和基因表达,以评估 BPA 的影响和 RSV 的潜在保护作用。结果表明,BPA 暴露显著增加了血清中 α-淀粉酶、α-葡萄糖苷酶、G6PC、胰岛素、HbA1c、HMG-CoA 还原酶、FFAs、TGs、DPP-4、MDA 和促炎细胞因子如 TNF-α 和 IL-6 的水平。同时,BPA 暴露导致抗氧化酶如过氧化氢酶 (CAT)、谷胱甘肽过氧化物酶 (GPx) 和超氧化物歧化酶 (SOD) 以及 GLUT4 和 HDL 胆固醇的水平降低。然而,RSV 与 BPA 联合给药可显著改善 BPA 暴露引起的生物标志物水平的这些改变。RSV 治疗有效降低了升高的 α-淀粉酶、α-葡萄糖苷酶、G6PC、胰岛素、HbA1c、HMG-CoA 还原酶、FFAs、TGs、DPP-4、MDA 和促炎细胞因子水平,同时增加了抗氧化酶、GLUT4 和 HDL 胆固醇的水平。此外,BPA 暴露抑制了葡萄糖激酶 (GCK)、胰岛素样生长因子 1 (IGF-1) 和葡萄糖转运蛋白 2 (GLUT2) 的 mRNA 表达,并上调了解偶联蛋白 2 (UCP2) 的 mRNA 表达,这些都是涉及葡萄糖代谢和胰岛素调节的关键生物标志物。相比之下,RSV 治疗有效恢复了这些生物标志物的改变 mRNA 表达,表明其有潜力调节转录途径并恢复正常代谢功能。总之,本研究结果强烈表明 RSV 作为治疗 BPA 诱导的代谢紊乱的一种有前途的治疗干预措施。通过减轻各种代谢途径的紊乱并调节与葡萄糖代谢和胰岛素调节相关的基因表达,RSV 显示出恢复正常代谢功能和抵抗 BPA 暴露引起的不良反应的潜力。然而,还需要进一步的研究来充分了解潜在的机制,并优化 RSV 治疗的剂量和持续时间以获得最大的治疗效果。